Solution of chemotherapeutic agents in ethylidene glycerol



weight.

. dene glycerol.

Patented Sept. 29, 1942 UNITED STATES PATENT 2,297,019 F cnnmornrwmmcSOLUTION AGENTS IN ETHYLIDENE GLYCEBOL No Drawing. Application August17, 1940, Serial no. 353,067

ficlaims.

This invention relates to solutions of chemotherapeutic agents inethylidene glycerol.

derivative) For the parenteral administration ofp-aminobenzenesulfonamide (sulfanilamide) or its derivatives, a solventmust be used which dissolves a relatively larger amount of thechemotherapeutic agent than does water; which does not produceanysub'stantial reaction with body tissue, and which is relativelynontoxic.

In accordance with this invention, sulfanila mide or its derivatives aredissolved in ethylidene glycerol and the resulting solution employed forthe parenteral administration of the desired chemotherapeutic agent.Pharmacological tests have demonstrated that ethylidene glycerol isadmirably suited for this purpose. While sulfanilamide is soluble inwater only to the exp aminobenzenesulfonphenylhydroxamide;p-acetylaminobenzenesulfonphenylhydroxamide; andp-aminobenzenesulfondimethylamide. The p-aminobenzenesulfondimethylamideis not so soluble in ethylidene glycerol as are the former derivatives.

Most of the derivatives of sulfanilamide are soluble to a marked degreein ethylidene glycerol. The solubillties of these different derivativesvary, but they are all many times more soluble in ethylidene glycerolthan they are in water.

The required dosage of the particular derivative can be administered ina concentration which causes a minimum of discomfort to the patient. Forexample, patients who cannot take the usual dose, 1.0 gram, ofsulfanilamide orally every four hours, now must be given subcutaneousinjections of 0.8 percent water solution of sulfanilamide. This requiresover 100 cc. of solution to administer 1 gram. It is possible todissolve this 1 gram of sulfanilamide in 5 cc. of ethylidene glycerol.

The volume of ethylidene glycerol employed to dissolve these substancesand other derivatives of sulfanilamide may be varied within wide limgramof body weight; intramuscularly 5.839:

0.5l9cc. per kilogram of body weight; and intravenously 351710.180 cc.per kilogram of body On subcutaneous or intramuscular injection,ethylidene produces but slight irritation.

Convenient therapeutic doses of the desired chemotherapeutic agent aredissolved in ethyli- This solution may be administered orally, rectally,or parenterally, preferably by the latter method, such as byintramuscular or intravenous administration.

Examples of sulfanilamide derivatives which may be dissolved inethylidene glycerol to form efiective therapeutic solutions are:2-(p-aminobenzenesulfonamido) thiazol; 2-(p-aminobenzenesulionamido)-4-methylthiazol; 2- (p-aminobenzenesulfonamido) e 4 phenylthiazol; N-trichloroacetyl aminobenzenesulfonamide; N -ubromopropionylaminobenzenesulfonamide; 2- (p-a-bromocaproyl aminobenzenesulionamido)pyridine; p-aminobenzenesulfon-hydroxamide; paminobenzenesulfonethanolamide; N -acety1- p aminobenzenesulfonamide; Nacetylaminobenzenesulfonamide (which has a very low activits. Preferablythe chemotherapeutic compound is completely dissolved in suflicientethylidene glycerol. Due to the marked solubility of sulfanilamide andits derivatives in the ethylidene glycerol, the usual dosage of thechemo therapeutic agent can be administered without unduly increasingthe volume. For' the comfort of the patient, it is undesirable toincrease the volume to too great an extent. The most desirable volumeemployed is dictated by the dosage required and the solubility of thesubstance in the ethylidene glycerol. A plurality of derivatives ofsulianilamide may be dissolved in the ethylidene glycerol foradministration to a patient. Likewise, other substances may be insolution in the ethylidene glycerol'as well as sulfanilamide or itsderivatives or a plurality of sulfanilamide compounds.

The solutions are relatively easily prepared; for example, 10 grams ofsulianilamide are dissolved in about 43 cc. of ethylidene glycerol withwarming. The solution is cooled and made up to 50 cc. volume withethylidene glycerol. This is filtered and is then ready for use aftersterilizing.

If a lesser concentration is required, the solution may be diluted withethylidene glycerol.

7 If 10 percent solutions of 2 (p-aminobenzena sulfonamido) -thiazol, N-trichloroacetyl aminoity and is less soluble than the N-trichloroacetyl benzenesulfonamide, or p-aminobenzenesulfonhyis made upto 100 cc. volume with ethylidene 10 glycerol. After filtering andsterilizing the solution is ready for use.

While preferred embodiments of this invention have been described,various modifications may be made therein without, departing from thescope 15 ot the appended claims.

What is claimed is:

1. A solution of a p-aminobenzenesulionamide in ethylidene glycerol.

2. A solution of a derivative of p-aminoben- 5 enemili'onamide inethylidene'glycerol.

3. A solution of p-aminobenzenesulfonamide in ethylidene glycerol.

4. A solution 01 an N -substituted p-aminobenzene-sulfonamide inethylidene glycerol.

5. A solution of Z-(p-aminobenzenesulionamido) pyridine in ethylideneglycerol.

'6. A solution of 2-(p-aminobenzenesuli'onamido) thiazol in ethylideneglycerol.

HORACE A. SHONLE.

